Certain organophosphorus compound (OPs) produce a delayed neurotoxic response in man, hen, and number of other species in which long axons degenerate in a distal-to-proximal pattern. The hen is currently regarded as the species of choice in experimental studies. Axonopathy has been postulated to be initiated by phosphorylation of a particular membrane-bound protein found in nervous tissue. This protein has been found to have esterase activity which is probably irrelevant to its function, although its physiologic and neuropathogenic roles are unknown. Since this receptor for neurotoxic OPs is usually assayed on the basis of its esteratic activity, it is generally referred to as "neurotoxic esterase" (NTE). Recently, NTE has been shown to exist in hen, rat, and human lymphocytes and rat and human platelets. There is a good correlation between inhibition of brain and lymphocyte NTE at 4 hr post dosing with axonopathic OPs in the hen. At 24 hr, the correlation appears to falter. Some nonaxonopathic OPs cause a stimulation of lymphocyte NTE at 4 hr. This project will examine the dose and time response of brain and lymphocyte heterophil/neutrophil, and platelet NTE in the hen and rat following dosing with axonopathic and nonaxonopathic OPs. The rat will be used primarily to allow the investigiation of the response in platelets. The leukocyte type showing the most reliable correlation with brain NTE inhibition will be selected for optimization of sampling, storage, and assay conditions for control human blood. The basis for the stimulation of leukocyte NTE by certain nonaxonopathic OPs will be investigated, as well as the subcellular distribution of NTE in these cells. It is hoped that this study will demonstrate the feasibility or nonfeasibility of using leukocyte NTE as a biomonitor of human exposure neurotoxic OPs, and that studies of subcellular distribution and stimulation of NTE in leukocytes will provide insight into the physiologic and pathogenic roles of this protein.